Programmable cells of monocytic origin as a source of osteochondroprogenitors: Effect of growth factors on osteogenic differentiation

We have demonstrated previously that peripheral blood monocytes can be converted in vitro to a multipotent stem cell-like cell termed programmable cell of monocytic origin (PCMO) and subsequently into cells with chondrocyte-like phenotype. Here, we investigated whether PCMO could also be differentiated into osteoblast-like cells using growth factors with known osteoinductive potency. Following stimulation with BMP-2, BMP-7, IGF-1 or TGF-β1 for 7 and 14 days, PCMOs were analyzed for mRNA expression of collagen types I and V, alkaline phosphatase, osteocalcin, runt-related transcription factor-2 (Runx2) and Osterix (Osx) by quantitative RT-PCR (qPCR) and the levels of collagen I in culture supernatants by ELISA. The expression of osteoblastic markers was evident, albeit at a different extent in cultures of PCMOs after treatment with the above-mentioned growth factors. Culture supernatants from PCMOs stimulated for 6-10 days with BMP-2, BMP-7, IGF-1 or TGF-β1 contained high levels of collagen type I, together with earlier data indicating synthesis and proper secretion. The findings suggest that PCMOs can transform into cells that are phenotypically similar to osteoblasts and identify these cells as osteochondroprogenitors. The possibility of differentiating PCMOs from peripheral blood in sizable quantities could be a novel way to obtain autologous bone-like substitutes without donor-site morbidity.